During postnatal development when the eye is still growing, a mechanism commonly referred to as the emmetropization mechanism uses the eye's refractive error to regulate the growth of the scleral shell to match the axial length of the eye t the focal plane. When functioning properly, this mechanism ensures that images will be sharply focused on the retina. The problem, for over 40% of Americans and up to 96% of groups in East Asia, is that the eye becomes too long for its own optics and is thus myopic. In addition to the cost (over $14 billion annually in the United States) of eye exams, glasses, contact lenses, and refractive surgery, even low amounts of myopia raise the risk of developing blinding conditions. Thus, effective strategies to slow eye growth and reduce the prevalence of juvenile-onset myopia in children are needed. Various strategies (bifocal glasses and contact lenses, muscarinic antagonist eye drops, scleral reinforcement surgery) have been developed to control axial elongation and myopia with limited success. An important problem is that we do not have a solid understanding of the visual cue or cues that are used by the emmetropization mechanism to determine if the eye is too short (hyperopia) and should increase its growth rate to achieve emmetropia, or if the eye is becoming too long (myopia) and should slow the axial elongation rate to match the maturation of the optics. We have developed a new theory of how the retina does this based on the temporal characteristics of fluctuations of in-focus vs. out-of-focus images experienced by photoreceptors and the neurons to which they connect. This has led us to discover two stimuli that have powerful effects on refractive development in young tree shrews, a cone-dominated dichromatic mammal closely related to primates: (1) Ambient long wavelength (628 10 nm) red light slows eye growth so that eyes remain hyperopic. We will test two hypotheses about the red-produced STOP signals that will not only improve our understanding of the emmetropization mechanism, but also will tell us if a form of this red stimulus has the potential to be developed as a method to slow myopia development in children. In specific aim 1 we will determine if the red light paradigm slows eye growth in juvenile tree shrews when used for as little as two hours per day and in older juvenile animals. In specific aim 2 we will determine if the red light paradigm can restrain the eye growth caused by wearing a minus lens, an established tool for inducing myopia in animals that may mimic human myopiagenic environments. We have also found (2) that ambient flickering short wavelength (464 10 nm) blue light containing many temporal frequencies is strongly myopiagenic. Further, interactions of the red and blue is stimuli can negate the effects of the red light, producing myopia. In specific aim 3 we will examine the blue/red temporal interactions that stimulate myopia. These may identify components of artificial lighting that should be avoided. The data collected in the proposed grant will potentially lead to a further proposal as an RO1.